Abstract: Fragile X syndrome (FXS) is the most common inherited form of autism and intellectual disability. Previous work has demonstrated impaired mGluR-dependent long-term depression (LTD) and long-term potentiation (LTP) in Fmr1 KO mice, the mouse model of FXS. Recent studies have shown hyperactivity of the overall neuronal circuit and hypoactivity of parvalbumin-positive fast-spiking interneurons in the primary visual cortex (V1) of Fmr1 KO mice. However, how experience affects synaptic and circuit plasticity in Fmr1 KO mice, and how impairments in these forms of plasticity may lead to the alterations in the visual perception and learning is poorly understood.  We have recently discovered a new form of visual familiarity-dependent oscillations. These oscillations can be blocked by the muscarinic receptor antagonists and may influence visual information processing in V1. To study how visual familiarity (a form of learning in V1) is impaired in Fmr1 KO mice, we have used a comprehensive approach including channelrhodopsin-2 assisted circuit mapping (CRACM) in visual cortex slices, in vivo extracellular recording using high-density silicon probes, pupillometry, and behavior. We have discovered attenuation in the duration and magnitude of the familiarity-induced oscillations and their frequency shift in Fmr1 KO mice. This attenuation was correlated with the decreased stimulus-specific adaptation of the transient pupil dilation, a biomarker of surprise response. We have identified an oscillatory neural circuit in V1 formed after the visual experience, which consisted of the intrinsically bursting (IB) layer 5 pyramidal cells, fast-spiking (FS) interneurons in layer 4 and layer 2/3 regular-spiking (RS) cells. Using a combination of in vivo directed information analysis and in vitro circuit mapping, we have discovered that the layer 5-layer 4 FS connection is weaker in Fmr1 KO mice which may serve as the underlying mechanism for the weaker oscillations in vivo.

Bio: Alexander Chubykin earned his M.S. degree in Applied Mathematics and Applied Physics from the Moscow Institute of Physics and Technology, Moscow, Russia. Dr. Chubykin then received his Ph.D. from the University of Texas Southwestern Medical Center, Dallas, TX in Neuroscience in 2006. During his graduate training with Nobel Laureate Dr. Thomas Sudhof,  Dr. Chubykin studied how synapses, connections between neurons, are established and stabilized by neuronal activity, and how this process is impaired in autism spectrum disorders (ASD’s). He completed his postdoctoral training with Dr. Mark Bear at the Massachusetts Institute of Technology, where he studied how the mouse visual cortex encodes time. In August 2014 Dr. Chubykin joined Purdue University with an appointment in the Department of Biological Sciences. 

~BME Faculty Host: Jacqueline Linnes~

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